Physiological studies have shown that substantial numbers of anatomically defined transmitter release elements may be non-functional. Such inactivated synapses represent a potential basis for modifiability or plasticity in neural systems. Excitatory amino acids elicit three distinct types of membrane conductance changes: a highly voltage sensitive response, a voltage independent conductance change, and an intermediate type of response. Glutamate elicits this latter response which can be shown to be due to joint activation of receptors responsible for the other two types of responses. Development of Na+ dependent mechanmisms underlying electrical excitability has been followed both biochemically with apropriate ligand binding assays and electrophysiologically. Na+ channels are present at very early times in vitro and increase in number and in their distribution over he neuronal surface with little change in kinetic properties. Opiate peptide receptor activation reduces excitatory transmitter release. Delta and kappa type receptors mediate this effect on spinal cord cells, while Mu receptors are essentially restricted to sensory neurons. Dorsal root ganglion (DRG) and ventral spinal cord (VSC) neurons were grown in a compartmented cell culture chamber such that their axonal protein composition could be compared after metabolic labelling and SDS-polyacrylamide gel electrophoresis. Distinct quantitative differences can be demonstrated with this system in a small number of axonal proteins when axons are co-cultured with neuroglial cells from the central or the peripheral nervous system. Two proteins were changed specifically by co-culture with peripheral, but not central neuroglial cells, whereas 5 proteins were specifically changed under the influence of central, but not peripheral, glial cells.